Is sunitinib plus transtuzumab safe and effective in patients with advanced breast cancer?

This paper studied the safety and efficacy of sunitinib (Sutent) in combination with trastuzumab (Herceptin) in the treatment of advanced breast cancer. 

Trastuzumab is used to treat metastatic (cancer that has spread to other parts of the body) breast cancer that is human epidermal growth factor receptor 2 (HER2) positive (elevated presence of HER2 protein on cancer cells).

Sunitinib a cancer drug that is currently used in renal cancer, gastrointestinal cancer and pancreatic cancer. Sunitinib works by inhibiting blood vessel growth (which the cancer needs to supply oxygen and nutrients) and blocking cell multiplication. It is thought that adding sunitinib to trastuzumab treatment may improve the outcomes of breast cancer.

Patients with locally recurrent (cancer that has returned to the original site) or metastatic HER2 positive breast cancer were studied. 57 patients received sunitinib with trastuzumab while 3 patients received trastuzumab only. The dose of sunitinib was adjusted based on each patient's response to the drug.

2 patients completed the study after 18 months of treatment while 58 patients discontinued treatment. Of the 58 patients who discontinued treatment, 44 did so due to worsening disease while 11 patients did so due to adverse event (undesired harmful effect due to drug).

Based on the 58 patients who received both trastuzumab and sunitinib, the overall response rate (decrease in tumour size) was 37%. The clinical benefit rate (percentage of tumours that decreases in size or remains the same size) was 56%. Overall, 75% of these patients had reductions in tumour size over the course of the study. At the average follow-up time of 24.4 months, the average time to progression of disease (worsening disease) was 6.4 months. The one year survival rate was 91%.

Of adverse events reported,  75% were of fatigue, 60% were of diarrhoea and 53% were of mouth disorders. Adverse events caused temporary treatment discontinuations or dose reductions of one or both study drugs in 48 patients. 40% of patients had adverse events related heart failure. This might be because cardiac dysfunction is a known side effect of trastuzumab and also associated with sunitinib. 

The authors concluded that sunitinib plus trastuzumab showed antitumor activity in patients with HER2 positive advanced breast cancer who had not received prior anthracycline therapy (chemotherapy with drugs such as Daunomycin or Adriamycin).

It is unlikely that this regimen will be further developed due to disappointing resulst in further trials. However the results contribute towards evaluating the feasibility of targeting both HER2 and blood vessel growth together in breast cancer.